Ozone-induced lung inflammation (steroid insensitive)

Model:

  • Airway exposure to Ozone produces a localised inflammation, characterised by an influx of neutrophils and mononuclear cells, which is steroid insensitive.

Background:

  • Ozone (O3), an oxidizing and highly toxic air pollutant, is associated with an immediate impairment of lung function and contributes to increased morbidity in patients with asthma and chronic obstructive pulmonary disease (COPD). When inhaled, ozone can cause cough, shortness of breath, and transient changes in breathing patterns. Short-term exposure to O3 induces influx of neutrophils and mast cells. The O3-induced acute pathological changes are characterized by an influx of neutrophils and development of airway hyperresponsiveness (AHR).
  • Neutrophilic inflammation, which is unresponsive to steroid treatment, is a key contributor in the pathogenesis of diseases such as Asthma, COPD and Acute Lung Injury, making this a useful model for screening compounds targeting these conditions.

Animal:

  • Rats

Inducer:

  • Ozone

Dosing routes:

  • P.O., I.P., I.T. S.C., I.N. and I.V.

Study Duration:

  • Approximately 4 weeks

Parameter Measures:

  • BALF cellular infiltration
  • Cytokines in the Blood/BALF
  • Oxidative stress assays
  • Histology
  • Organ or fluid collection for external analysis e.g. PK analysis
  • Western Blot
  • PCR

Cell Data

Ozone - neutrophils    Ozone - monocytes

Oxidative Stress analysis

Ozone - GSH

BALF Cytokine Data

Ozone - IL-1B    Ozone - TNF-a

# = compared to Air exposed group and * = compared to Ozone + Vehicle group